Cartilage oligomeric matrix protein is a non-collagenous extracellular matrix protein expressed in cartilage, ligament, and tendon and encoded by the COMP gene. Mutations in the COMP gene cause the skeletal dysplasias pseudoachondroplasia and multiple epiphyseal dysplasia. See, for example, Posey, K L: “The role of cartilage oligomeric matrix protein (COMP) in skeletal disease,” Curr. Drug Targets. 2008 October; 9(10):869-77. Pseudoachondroplasia is an inhereited bone growth disorder. Individuals having pseudoachondroplasia generally have a short stature with the average height of both males and females under 48 inches. Additionally, individuals with pseudoachondroplasia experience joint pain in adolescence that progresses to osteoarthritis in adulthood. Multiple epiphyseal dysplasia affects the epiphyses, the ends of the long bones in the arms and legs. Symptoms of multiple epiphyseal dysplasia include joint pain, early-onset arthritis, and in some cases mild short stature and/or a waddling walk. Both dysplasias pseudoachondroplasia and multiple epiphyseal dysplasia stem from the intracellular retention of cartilage oligomeric matrix protein in the enlarged rough endoplasmic reticulum. The retention of cartilage oligomeric matrix protein causes chondrocyte cell death which decreases linear bone growth. The retention of cartilage oligomeric matrix protein also reduces the stability of the extracellular matrix, which causes abnormalities in the extracellular matrix and makes the extracellular matrix erode during normal physical activity. Additionally, increased serum cartilage levels of cartilage oligomeric matrix protein are found in patients with aggressive arthritis.
Antisense compounds have been used to modulate target nucleic acids. Antisense compounds comprising a variety of chemical modifications and motifs have been reported. In certain instances, such compounds are useful as research tools, diagnostic reagents, and as therapeutic agents. In certain instances antisense compounds have been shown to modulate protein expression by binding to a target messenger RNA (mRNA) encoding the protein. In certain instances, such binding of an antisense compound to its target mRNA results in cleavage of the mRNA. Antisense compounds that modulate processing of a pre-mRNA have also been reported. Such antisense compounds alter splicing, interfere with polyadenlyation or prevent formation of the 5′-cap of a pre-mRNA.